UK has begun using drugs for covid-19 cases before they become severe

By Clare Wilson

People in the UK who are at higher risk for covid-19 can now help trial the first antiviral pill for this infection that can be taken at home, while those who are classed as extremely vulnerable can get antibody infusions as soon as they test positive.

“These are potentially game-changing drugs,” says Philip Evans at the UK National Institute for Health Research. So how will the new treatments be delivered and how effective are they?

When the pandemic began, doctors had no treatments for covid-19 other than general supportive care, such as giving people oxygen. Then, certain drug treatments became available, but they have mostly focused on tackling severe symptoms and have had to be given in hospital settings.

Throughout 2021, though, new treatments were developed that are intended for use when a person first becomes infected and symptoms are still mild. The hope is that by giving such medicines as soon as possible after a positive test, people are less likely to get sick enough to need a hospital stay.

Sotrovimab and molnupiravir

In the UK, people who are most vulnerable to covid-19 should by now have received letters containing a PCR test and advice that if they develop symptoms, they should take the test and call a special clinic to discuss treatment. This includes people with cancer, people with Down’s syndrome or those with very weak immune systems.

About 70 hospital clinics called Covid Medicines Delivery Units have been set up around the UK to help these groups. The main treatment on offer is an intravenous therapy called sotrovimab, an artificial antibody designed to block the coronavirus. A different antibody mixture called Ronapreve had originally been planned for use, but early lab tests suggest this is less effective against the omicron variant, while sotrovimab maintains enough efficacy to be useful.

The clinics also offer an oral treatment, called molnupiravir, which trials found cut hospital admissions by 30 per cent if taken within the first five days after infection.

The pill was made available in the UK in December through a mass trial for people not classed as extremely vulnerable, but who are still at somewhat higher risk from covid-19. This includes those 50 and over, or 18 and over with a medical condition such as diabetes or severe asthma.

While the UK was the first country to approve molnupiravir, in November, the health services decided a further 10,000-person trial is needed, to see how effective the drug is in a highly vaccinated population as the omicron variant spreads through the UK.

Half of those who sign up are being couriered a five-day course of molnupiravir, while the rest get no extra treatment. Anyone can sign up for it on a website if they have had symptoms begin in the past five days, have had a positive lateral flow or PCR test and meet the risk criteria.

With the UK in the middle of an omicron surge, 700 people have so far joined the trial and some results are expected in the next few months, says Evans. If molnupiravir is found to be beneficial when used like this, the plan is for it to be prescribed by family doctors the way that GPs prescribe many other drugs.

Molnupiravir has potential downsides, though. It works by introducing mutations in virus DNA, so anyone pregnant or breastfeeding cannot take it in case it harms their fetus or baby. Participants capable of getting pregnant will be sent a pregnancy test and must use contraception.

Another concern is that the viral mutations could lead to the emergence of dangerous new variants or drug resistance. Researchers are genetically sequencing virus samples from those taking the medicine to check for this.

David Lowe at University College London, who is involved in the trial, says mutations aren’t a big worry. “Once you’ve given for a few days, the level of infectious virus is so low that you can’t even culture it. But it is something that we need to keep an eye on,” he says.

Paxlovid

The mass trial, which is called Panoramic, is an unusual “platform” design, in that if further antiviral drugs or antibodies are approved, they can be slotted in. This may happen soon with another antiviral oral pill called Paxlovid, which may reduce the risk of developing severe covid-19 by nearly 90 per cent.

Paxlovid consists of a drug that blocks an enzyme the coronavirus needs to reproduce – a similar mechanism to some anti-HIV drugs – as well as another compound that slows the drug’s breakdown. Paxlovid is currently under review for approval in the UK. The US Food and Drug Administration gave the drug emergency approval on 22 December.

Evans points out, however, that the eye-catching 90 per cent efficacy results reported for the drug haven’t yet been fully scrutinised by independent scientists in a peer-reviewed paper. The initial results for molnupiravir suggested it had 50 per cent efficacy, but this later fell to 30 per cent. “That’s why [scrutiny] is really important,” says Evans.

Looking ahead

“Vaccines will remain the cornerstone of our fight against covid-19, but with various new variants coming along, the oral [treatments] may well have a very important part to play in the next year,” says Evans.

In 2022, the Panoramic trial will expand to give antivirals to household contacts of people with covid-19, an approach known as post-exposure prophylaxis. Another addition to the trial could be a long-acting antibody injection called Evusheld, which was approved in the US in December.

Evusheld is thought to give protection against infection for up to six months and is aimed at people with weak immune systems or those who have had bad reactions to covid-19 vaccines or their ingredients.

“If one or more [of these treatments] is proven to be effective and safe in the community, it would add a new weapon in the armoury against covid-19,” says Evans.